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Metal-organic frameworks (MOFs) are a class of multifunctional organometallic compounds that include metal ions combined with assorted organic linkers. Recently, these compounds have received widespread attention in medicine, due to their exceptional qualities, including a wide surface area, high porosity, outstanding biocompatibility, non-toxicity, etc. Such characteristic qualities make MOFs superb candidates for biosensing, molecular imaging, drug delivery, and enhanced cancer therapies. This review illustrates the key attributes of MOFs and their importance in cancer research. The structural and synthetic aspects of MOFs are briefly discussed with primary emphasis on diagnostic and therapeutic features, as well as their performance and significance in modern therapeutic methods and synergistic theranostic strategies including biocompatibility. This review offers cumulative scrutiny of the widespread appeal of MOFs in modern-day oncological research, which may stimulate further explorations.

Volume scanning electron microscopy (VSEM) involves the serial sectioning and imaging of a sample using scanning electron microscopy (SEM), followed by segmentation and three-dimensional (3D) reconstruction using computer software packages to allow visualization of 3D structures. VSEM can reveal qualitative and quantitative properties of organelles and cells within tissues at nanoscale. The ability to visualize spatial relationships of structures of interest within and across cells in 3D space in particular sets VSEM apart from conventional SEM and transmission electron microscopy. Here, we provide an overview of VSEM platforms and image processing, highlighting characteristics that will aid selection of a method to address specific research questions in dermatological research., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The development of nanomaterials with therapeutic and/or diagnostic properties has been an active area of research in biomedical sciences over the past decade. Nanomaterials have been identified as significant medical tools with potential therapeutic and diagnostic capabilities that are practically impossible to accomplish using larger molecules or bulk materials. Fabrication of nanomaterials is the most effective platform to engineer therapeutic agents and delivery systems for the treatment of cancer. This is mostly due to the high selectivity of nanomaterials for cancerous cells, which is attributable to the porous morphology of tumour cells which allows nanomaterials to accumulate more in tumour cells more than in normal cells. Nanomaterials can be used as potential drug delivery systems since they exist in similar scale as proteins. The unique properties of nanomaterials have drawn a lot of interest from researchers in search of new chemotherapeutic treatment for cancer. Metal sulfide nanomaterials have emerged as the most used frameworks in the past decade, but they tend to aggregate because of their high surface energy which triggers the thermodynamically favoured interaction. Stabilizing agents such as polymer and microgels have been utilized to inhibit the particles from any aggregations. In this review, we explore the development of metal sulfide polymer/microgel nanocomposites as therapeutic agents against cancerous cells.

2D monolayer gastric organoids (2DMGOs)-on-a-chip have consistent structures and can live for more than a year in culture. This state-of-the-art cell physiological system in a microfluidic device provides a way to investigate biomedically relevant, stimuli-dependent cellular responses in a variety of differentiated 2DMGOs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: In an effort to mitigate COVID-19 related challenges for clinical research, the US Food and Drug Administration (FDA) issued new guidance for the conduct of 'virtual' clinical trials in late March 2020. This study documents trends in the use of connected digital products (CDPs), tools that enable remote patient monitoring and telehealth consultation, in clinical trials both before and after the onset of the pandemic., Design: We applied a comprehensive text search algorithm to clinical trial registry data to identify trials that use CDPs for remote monitoring or telehealth. We compared CDP use in the months before and after the issuance of FDA guidance facilitating virtual clinical trials., Setting: All trials registered on ClinicalTrials.gov with start dates from May 2019 through February 2021., Outcome Measures: The primary outcome measure was the overall percentage of CDP use in clinical trials started in the 10 months prior to the pandemic onset (May 2019-February 2020) compared with the 10 months following (May 2020-February 2021). Secondary outcome measures included CDP usage by trial type (interventional, observational), funder type (industry, non-industry) and diagnoses (COVID-19 or non-COVID-19 participants)., Results: CDP usage in clinical trials increased by only 1.65 percentage points, from 14.19% (n=23 473) of all trials initiated in the 10 months prior to the pandemic onset to 15.84% (n=26 009) of those started in the 10 months following (p<0.01). The increase occurred primarily in observational studies and non-industry funded trials and was driven entirely by CDP usage in trials for COVID-19., Conclusions: These findings suggest that in the short-term, new options created by regulatory guidance to stimulate telehealth and remote monitoring were not widely incorporated into clinical research. In the months immediately following the pandemic onset, CDP adoption increased primarily in observational and non-industry funded studies where virtual protocols are likely medically necessary due to the participants' COVID-19 diagnosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: By 2050, almost 5 billion people globally are projected to have myopia, of whom 20% are likely to have high myopia with clinically significant risk of sight-threatening complications such as myopic macular degeneration. These are diagnoses that typically require specialist assessment or measurement with multiple unconnected pieces of equipment. Artificial intelligence (AI) approaches might be effective for risk stratification and to identify individuals at highest risk of visual loss. However, unresolved challenges for AI medical studies remain, including paucity of transparency, auditability, and traceability., Methods: In this retrospective multicohort study, we developed and tested retinal photograph-based deep learning algorithms for detection of myopic macular degeneration and high myopia, using a total of 226 686 retinal images. First we trained and internally validated the algorithms on datasets from Singapore, and then externally tested them on datasets from China, Taiwan, India, Russia, and the UK. We also compared the performance of the deep learning algorithms against six human experts in the grading of a randomly selected dataset of 400 images from the external datasets. As proof of concept, we used a blockchain-based AI platform to demonstrate the real-world application of secure data transfer, model transfer, and model testing across three sites in Singapore and China., Findings: The deep learning algorithms showed robust diagnostic performance with areas under the receiver operating characteristic curves [AUC] of 0·969 (95% CI 0·959-0·977) or higher for myopic macular degeneration and 0·913 (0·906-0·920) or higher for high myopia across the external testing datasets with available data. In the randomly selected dataset, the deep learning algorithms outperformed all six expert graders in detection of each condition (AUC of 0·978 [0·957-0·994] for myopic macular degeneration and 0·973 [0·941-0·995] for high myopia). We also successfully used blockchain technology for data transfer, model transfer, and model testing between sites and across two countries., Interpretation: Deep learning algorithms can be effective tools for risk stratification and screening of myopic macular degeneration and high myopia among the large global population with myopia. The blockchain platform developed here could potentially serve as a trusted platform for performance testing of future AI models in medicine., Funding: None., Competing Interests: Declaration of interests DSWT and TYW are co-inventors, with patents pending, for a deep learning system for diabetic retinopathy, glaucoma, and age-related macular degeneration (SG Non-Provisional Application number 10201706186V), and a computer-implemented method for training an image classifier using weakly annotated training data (SG Provisional Patent Application number 10201901083Y), and are co-founders and shareholders of EyRIS, Singapore. HLin has a patent pending for a system and method for medical data sharing using blockchain technology (distinct from the blockchain platform presented in this study; patent number CN: 202011401658.5). THR has two patents pending relating to cardiovascular and cardio-cerebrovascular disease and eye images (cardiovascular disease diagnosis assistant method and apparatus: 10–2018–0166720(KR), 10–2018–0166721(KR), 10–2018–0166722(KR), PCT/KR2018/016388; and method for predicting cardio-cerebrovascular disease using eye image: 10–2017–0175865(KR), and was a scientific advisor to and is a stockholder for Medi Whale. YLW is an employee of Essilor International. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Flow cytometry is a popular technique used for both clinical and research purposes. It involves laser-based technology to characterize cells based on size, shape, and complexity. Additionally, flow cytometers are equipped with the ability to take fluorescence measurements at multiple wavelengths. This capability makes the flow cytometer a practical resource in the utilization of fluorescently conjugated antibodies, fluorescent proteins, DNA binding dyes, viability dyes, and ion indicator dyes. As the technology advances, the number of parameters a flow cytometer can measure has increased tremendously, and now some has the capacity to analyze 30-50 or more parameters on a single cell. Here, we describe the basic principles involved in the mechanics and procedures of flow cytometry along with an insight into applications of flow cytometry techniques for biomedical and allergic disease research.

Female mosquitoes need a blood meal to reproduce, and in obtaining this essential nutrient they transmit deadly pathogens. Although crucial for the spread of mosquito-borne diseases, blood feeding remains poorly understood due to technological limitations. Indeed, studies often expose human subjects to assess biting behavior. Here, we present the biteOscope, a device that attracts mosquitoes to a host mimic which they bite to obtain an artificial blood meal. The host mimic is transparent, allowing high-resolution imaging of the feeding mosquito. Using machine learning, we extract detailed behavioral statistics describing the locomotion, pose, biting, and feeding dynamics of Aedes aegypti, Aedes albopictus, Anopheles stephensi, and Anopheles coluzzii . In addition to characterizing behavioral patterns, we discover that the common insect repellent DEET repels Anopheles coluzzii upon contact with their legs. The biteOscope provides a new perspective on mosquito blood feeding, enabling the high-throughput quantitative characterization of this lethal behavior., Competing Interests: FH, LL, MP No competing interests declared, (© 2020, Hol et al.)

The multifaceted ability to produce, transmit, receive, and respond to acoustic signals is widespread in animals and forms the basis of the interdisciplinary science of bioacoustics. Bioacoustics research methods, including sound recording and playback experiments, are applicable in cognitive research that centers around the processing of information from the acoustic environment. We provide an overview of bioacoustics techniques in the context of cognitive studies and make the case for the importance of bioacoustics in the study of cognition by outlining some of the major cognitive processes in which acoustic signals are involved. We also describe key considerations associated with the recording of sound and its use in cognitive applications. Based on these considerations, we provide a set of recommendations for best practices in the recording and use of acoustic signals in cognitive studies. Our aim is to demonstrate that acoustic recordings and stimuli are valuable tools for cognitive researchers when used appropriately. In doing so, we hope to stimulate opportunities for innovative cognitive research that incorporates robust recording protocols. This article is categorized under: Neuroscience > Cognition Psychology > Theory and Methods Neuroscience > Behavior Neuroscience > Cognition., (© 2020 Wiley Periodicals LLC.)

The actinomycetes are Gram-positive bacteria belonging to the order Actinomycetales within the phylum Actinobacteria . They include members with significant economic and medical importance, for example filamentous actinomycetes such as Streptomyces species, which have a propensity to produce a plethora of bioactive secondary metabolites and form symbioses with higher organisms, such as plants and insects. Studying these bacteria is challenging, but also fascinating and very rewarding. As a Microbiology Society initiative, members of the actinomycete research community have been developing a Wikipedia-style resource, called ActinoBase, the purpose of which is to aid in the study of these filamentous bacteria. This review will highlight 10 publications from 2019 that have been of special interest to the ActinoBase community, covering 4 major components of actinomycete research: (i) development and regulation; (ii) specialized metabolites; (iii) ecology and host interactions; and (iv) technology and methodology.

Background: Transcranial direct current stimulation (tDCS) is a method of noninvasive neuromodulation and potential therapeutic tool to improve functioning and relieve symptoms across a range of central and peripheral nervous system conditions. Evidence suggests that the effects of tDCS are cumulative with consecutive daily applications needed to achieve clinically meaningful effects. Therefore, there is growing interest in delivering tDCS away from the clinic or research facility, usually at home., Objective: To provide a comprehensive guide to operationalize safe and responsible use of tDCS in home settings for both investigative and clinical use., Methods: Providing treatment at home can improve access and compliance by decreasing the burden of time and travel for patients and their caregivers, as well as to reach those in remote locations and/or living with more advanced disabilities., Results: To date, methodological approaches for at-home tDCS delivery have varied. After implementing the first basic guidelines for at-home tDCS in clinical trials, this work describes a comprehensive guide for facilitating safe and responsible use of tDCS in home settings enabling access for repeated administration over time., Conclusion: These guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting., Competing Interests: Declaration of competing interest Authors Leigh Charvet, Michael Shaw, Adam Woods, and Helena Knotkova declare no conflicts of interest. The City University of New York (CUNY) has IP on a neurostimulation system and methods with Marom Bikson as inventor. Marom Bikson has equity in Soterix Medical Inc and serves as a consultant for Boston Scientific, GHK, and Mecta., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The association between an action and its sensory consequence has been linked to our sense of agency (SoA). While ecological validity is crucial in investigating such a complex phenomenon, previous paradigms focusing on the cortical analysis of movement-related images used simplified experimental protocols. Here, we examined the influence of action-associated predictive processes on visual event-related potentials (ERPs) in a paradigm that models everyday actions more precisely, using a commercial gesture control device, ecological stimuli depicting a human hand and a behavioural training to reinforce the sense of control over action outcomes. We assessed whether a more natural setup would result in robust ERP modifications following self-initiated movements relative to passive viewing of the same images. We found no compelling evidence for amplitude modulation for the early occipital C1 and P1 components. Crucially, we observed strong action-associated amplitude enhancement for the posterior N1, an effect that was not present in our previous study that relied on conventional button-presses. We propose that the N1 effect in our ecologically more valid paradigm can either reflect stronger attentional amplification of domain-specific visual processes following self-initiated actions, or indicate that sensory predictions in the visual N1 latency range manifest in larger (rather than reduced) ERPs. Overall, our novel approach utilizing a gesture-control device can be a potent tool for investigating the behavioural and neural manifestations of SoA in the visual modality., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In this study, we show how defocused spatially offset Raman spectroscopy (SORS) can be employed to recover chemical information from media of biomedical significance within sealed plastic transfusion and culture bags using a commercial SORS instrument. We demonstrate a simple approach to recover subsurface spectral information through a transparent barrier by optimizing the spatial offset of the defocused beam. The efficiency of the measurements is assessed in terms of the SORS ratio and signal-to-noise ratio (S/N) through a simple manual approach and an ordinary least squares model. By comparing the results for three different biological samples (red blood cell concentrate, pooled red cell supernatant and a suspension of Jurkat cells), we show that there is an optimum value of the offset parameter which yields the maximum S/N depending on the barrier material and optical properties of the ensemble contents. The approach was developed in the context of biomedical applications but is generally applicable to any three-layer system consisting of turbid content between transparent thin plastic barriers (i.e., front and back bag surfaces), particularly where the analyte of interest is dilute or not a strong scatterer.

Recently, interest in the effects of radio frequency (RF) on biological systems has increased and is partially due to the advancements and increased implementations of RF into technology. As research in this area has progressed, the reliability and reproducibility of the experiments has not crossed multidisciplinary boundaries. Therefore, as researchers, it is imperative to understand the various exposure systems available as well as the aspects, both electromagnetic and biological, needed to produce a sound exposure experiment. This systematic review examines common RF exposure methods for both in vitro and in vivo studies. For in vitro studies, possible biological limitations are emphasized. The validity of the examined methods, for both in vitro and in vivo, are analyzed by considering the advantages and disadvantages of each. This review offers guidance for researchers to assist in the development of an RF exposure experiment that crosses current multidisciplinary boundaries.

Microfluidic systems (MFS) provide a range of advantages in biomedical applications, including improved controllability of material characteristics and lower consumption of reagents, energy, time and money. Fabrication of MFS employs various materials, such as glass, silicon, ceramics, paper, and metals such as gold, copper, aluminum, chromium and titanium. In this review, gold thin film microfluidic channels (GTFMFC) are discussed with reference to fabrication methods and their diverse use in chemical and biomedical applications. The advantages of gold thin films (GTF) include flexibility, ease of manufacture, adhesion to polymer surfaces, chemical stability, good electrical conductivity, surface plasmon resonance effects, ability to be chemically functionalized, etc. Various electroactuators and electroanalytical devices can incorporate GTF. GTF-based MFS have been used in environmental monitoring, assays of biomarkers, immunoassays, cell culture studies and pathogen identification.

We investigated whether motion sickness analogous to carsickness can be studied in a moving base simulator, despite the limited motion envelope. Importantly, to avoid simulator sickness, vision outside the simulator cabin was restricted. Participants (N = 16) were exposed blindfolded to 15-min lateral sinusoidal motion at 0.2 Hz and 0.35 Hz on separate days. These conditions were selected to realize optimal provocativeness of the stimulus given the simulator's maximum displacement and knowledge on frequency-acceleration interactions for motion sickness. Average motion sickness on an 11-point scale was 2.21 ± 1.97 for 0.2 Hz and 1.93 ± 1.94 for 0.35 Hz. The motion sickness increase over time was comparable to that found in studies using actual vehicles. We argue that motion base simulators can be used to incite motion sickness analogous to carsickness, provided considerable restrictions on vision. Future research on carsickness, potentially more prevalent in autonomous vehicles, could benefit from employing simulators., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The growing commercialization of scientific research has raised important concerns about industry bias. According to some evidence, so-called industry bias can affect the integrity of the science as well as the direction of the research agenda. I argue that conceptualizing industry's influence in scientific research in terms of bias is unhelpful. Insofar as industry sponsorship negatively affects the integrity of the research, it does so through biasing mechanisms that can affect any research independently of the source of funding. Talk about industry bias thus offers no insight into the particular epistemic shortcomings at stake. If the concern is with the negative effects that industry funding can have on the research agenda, conceptualizing this influence as bias obscures the ways in which such impact is problematic and limits our ability to offer solutions that can successfully address the concerns raised by the growing role of private funding in science.

Background: In 1997 the "Wessex Research Network (WReN) Spider" was developed and validated to assess the research experience of general practice based researchers. This bibliometric study traces the use and development of this instrument over 15 years., Methods: We performed a bibliographic search to identify all the citations of the original article since 2002., Results: Thirty one relevant papers were found. Publications were classified according to whether they used (N = 18) or cited (N = 13) the WReN Spider. The majority of these papers came from Australia (N = 18) and 10 papers focussed on the research training of Allied Health Professionals. The WReN Spider was used in 12 studies to assess baseline experience before a training intervention or to compare before and after training scores. The WReN Spider was often (N = 9) modified to additionally assess interest, confidence or interest in up-skilling in each of its 10 limbs. It was also often (N = 14) used in tandem with open ended questions to gain a more detailed understanding of people's research skills, or with additional questions focussing on the research context, culture and team. None of the papers confirmed the validation of the WReN Spider, although it was applied in contexts that differed from the one in which it was developed., Conclusions: The WReN Spider continues to be used to measure the research experience of health care practitioners, but it is frequently enhanced with other questions to look at the wider issues of research success, including collaborators, resource and environment.

Wearable automated seizure detection devices offer a high potential to improve seizure management, through continuous ambulatory monitoring, accurate seizure counts, and real-time alerts for prompt intervention. More importantly, these devices can be a life-saving help for people with a higher risk of sudden unexpected death in epilepsy (SUDEP), especially in case of generalized tonic-clonic seizures (GTCS). The Embrace and E4 wristbands (Empatica) are the first commercially available multimodal wristbands that were designed to sense the physiological hallmarks of ongoing GTCS: while Embrace only embeds a machine learning-based detection algorithm, both E4 and Embrace devices are equipped with motion (accelerometers, ACC) and electrodermal activity (EDA) sensors and both the devices received medical clearance (E4 from EU CE, Embrace from EU CE and US FDA). The aim of this contribution is to provide updated evidence of the effectiveness of GTCS detection and monitoring relying on the combination of ACM and EDA sensors. A machine learning algorithm able to recognize ACC and EDA signatures of GTCS-like events has been developed on E4 data, labeled using gold-standard video-EEG examined by epileptologists in clinical centers, and has undergone continuous improvement. While keeping an elevated sensitivity to GTCS (92-100%), algorithm improvements and growing data availability led to lower false alarm rate (FAR) from the initial ˜2 down to 0.2-1 false alarms per day, as showed by retrospective and prospective analyses in inpatient settings. Algorithm adjustment to better discriminate real-life physical activities from GTCS, has brought the initial FAR of ˜6 on outpatient real life settings, down to values comparable to best-case clinical settings (FAR < 0.5), with comparable sensitivity. Moreover, using multimodal sensing, it has been possible not only to detect GTCS but also to quantify seizure-induced autonomic dysfunction, based on automatic features of abnormal motion and EDA. The latter biosignal correlates with the duration of post-ictal generalized EEG suppression, a biomarker observed in 100% of monitored SUDEP cases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

: The accurate assessment of sleep is critical to better understand and evaluate its role in health and disease. The boom in wearable technology is part of the digital health revolution and is producing many novel, highly sophisticated and relatively inexpensive consumer devices collecting data from multiple sensors and claiming to extract information about users' behaviors, including sleep. These devices are now able to capture different biosignals for determining, for example, HR and its variability, skin conductance, and temperature, in addition to activity. They perform 24/7, generating overwhelmingly large data sets (big data), with the potential of offering an unprecedented window on users' health. Unfortunately, little guidance exists within and outside the scientific sleep community for their use, leading to confusion and controversy about their validity and application. The current state-of-the-art review aims to highlight use, validation and utility of consumer wearable sleep-trackers in clinical practice and research. Guidelines for a standardized assessment of device performance is deemed necessary, and several critical factors (proprietary algorithms, device malfunction, firmware updates) need to be considered before using these devices in clinical and sleep research protocols. Ultimately, wearable sleep technology holds promise for advancing understanding of sleep health; however, a careful path forward needs to be navigated, understanding the benefits and pitfalls of this technology as applied in sleep research and clinical sleep medicine.

Light microscopy has played a central role in science for the past couple of hundred years and will continue to do so. Multiple super-resolution microscopy techniques have been in the headlines for smashing what for more than 100+ years was believed to be the limits of optical microscopy. This resolution improvement enables the visualization of molecular structures and processes on the nano scale. While certain scientific questions in toxicology can benefit from modalities within the super-resolution suite, due diligence is required for efficiency and to achieve optimal results. For a given hypothesis being tested, there are biophysical issues that need to be considered before heading down the super-resolution road. All commercially available super-resolution modalities, along with cautions and tips, will be discussed. © 2019 by John Wiley & Sons, Inc., (© 2019 John Wiley & Sons, Inc.)

Objective To develop and verify a medical microdevice for analyzing the three-dimensional(3D)migration of tumor cells in extracellular matrix. Methods The mold of the microdevice was made by precision machining,and then the medical microdevice based on polydimethylsiloxane(PDMS)-glass was obtained by PDMS casting,moulding,and bonding.During the analysis,the suspension of tumor cells and matrigel were mixed and then added into the migration channel of microdevice,and the controllable migration of tumor cells in matrigel was induced by establishing chemokine concentration gradient on both sides of the migration channel.Meanwhile,the migration process of tumor cells was recorded with the live cell dynamic imaging device. Results Breast cancer cell line MCF-7 was taken as an example to verify the feasibility of the microdevice to control and dynamically monitor the 3D migration process of tumor cells in vitro.Qualitative analysis of imaging data showed that the migration of MCF-7 cell lines in matrigel was determined by the concentration gradient distribution direction of chemokine and presented as the amoeboid-like migration mode.The proportion and migration velocity of MCF-7 cells could be quantified by the quantitative analysis of cell migration process.The inhibition ability of matrix metalloproteinase inhibitors(Batimastat)and adenosine triphosphatase inhibitors(Blebbistation)on the 3D migration behavior of MCF-7 cells was found to be different. Conclusion This device can be used for in-depth analysis of tumor cell migration and its mechanism and for evaluating the efficacy of anti-metastatic drugs.

Life science research has been actively carried out in space for a long time using bioreactor equipment, in anticipation of manned space exploration and space tourism. Such studies have reported that the microgravity environment has a negative effect on the human body, including the musculoskeletal system, nervous system, and endocrine system. Bone loss and muscular atrophy are issues that need to be resolved before long-term exposure of the human body to a space environment. To address this problem, Y. K. Kim et al. designed a system in 2015 and performed an evaluation of an automated bioreactor development model (DM) for space experiments. In this study, we developed an automated bioreactor engineering model (EM) based on the previous literature, and conducted media exchange performance testing using the Bradford assay. We used a novel method that allowed quantitative assessment of the media exchange rate versus the conventional assessment method using visual observation with a camera. By measuring the media exchange rate of the automated bioreactor EM, we attempted to verify applicability for the system for space experiments. We expect that the experimental method proposed in this study is useful for logical determination of liquid exchange or circulation in different closed systems.

Injuries sustained due to attacks from explosive weapons are multiple in number, complex in nature, and not well characterised. Blast may cause damage to the human body by the direct effect of overpressure, penetration by highly energised fragments, and blunt trauma by violent displacements of the body. The ability to reproduce the injuries of such insults in a well-controlled fashion is essential in order to understand fully the unique mechanism by which they occur, and design better treatment and protection strategies to alleviate the resulting poor long-term outcomes. This paper reports a range of experimental platforms that have been developed for different blast injury models, their working mechanism, and main applications. These platforms include the shock tube, split-Hopkinson bars, the gas gun, drop towers and bespoke underbody blast simulators., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Mobile applications (apps) can bring health research and its potential downstream benefits closer to underserved populations. Drawing on experience developing an app for detecting and referring cases of cutaneous leishmaniasis in Colombia, called Guaral/app, we review key steps in creating such mobile health (mHealth) tools. These require consideration of the sociotechnical context using methods such as systems analysis and human-centered design (HCD), predicated on engagement and iteration with all stakeholders. We emphasize usability and technical concerns and describe the interdependency of technical and human considerations for mHealth systems in rural communities., Competing Interests: The authors have declared that no competing interests exist.

Purpose of Review: The integration of wearable devices and mobile health (mHealth) technology to facilitate behavior change has the potential to transform the efficacy of interventions and implementation programs for weight maintenance. The purpose of this review was to provide a comprehensive analysis of the overall utility of wearable devices for assessing and promoting weight maintenance in research and clinical settings., Recent Findings: Recent intervention trials using wearable devices have been successful in increasing physical activity and decreasing or maintaining body weight, but complex study designs involving multiple behavioral strategies make it difficult to assess whether wearable devices can independently influence weight status. The daily feedback that wearable devices and mHealth technology provide may assist in motivating higher levels of physical activity achievement. However, the integration of wearable devices into the healthcare setting and implementation of mHealth programs still need to be tested., Summary: Recent studies add concrete implications for providers and researchers to better assess and promote physical activity in healthcare settings by identifying how wearable devices can be advantageous for physical activity and health promotion.

The objective of this study was to develop and validate a novel 3D dynamic model of a pelvic side-impactor system. The biomechanical responses of a pelvic flexible model (having .mnf file suffix) under the lateral impact load for predicting the bone fracture mechanism are investigated as well. The 3D solid model of the side-impactor system was imported into MSC/ADAMS software for analyzing the dynamic model, and the pelvic flexible model was extracted from the CT images of a Chinese female volunteer. The flexible model of the pelvis system was developed considering a wide range of mechanical properties in the bone complex and soft tissue to achieve a realistic biomechanical response during a lateral impact. Good agreements were achieved between the dynamic simulations and the experimental results of pelvic side impacts, in terms of the biomechanical criteria. The dynamic model of impactor system could be employed to investigate the hip protector effectiveness, improving the vehicle safety, and biomechanical response of the other human organs.

Objective: The behavioral validation of an advanced driving simulator for its use in evaluating passive level crossing countermeasures was performed for stopping compliance and speed profile., Background: Despite the fact that most research on emerging interventions for improving level crossing safety is conducted in a driving simulator, no study has validated the use of a simulator for this type of research., Method: We monitored driver behavior at a selected passive level crossing in the Brisbane region in Australia for 3 months ( N = 916). The level crossing was then replicated in an advanced driving simulator, and we familiarized participant drivers ( N = 54) with traversing this crossing, characterized by low road and rail traffic., Results: We established relative validity for the stopping compliance and the approach speed., Conclusion: This validation study suggests that driving simulators are an appropriate tool to study the effects of interventions at passive level crossing with low road and rail traffic, which are prone to reduced compliance due to familiarity., Application: This study also provides support for the findings of previous driving simulator studies conducted to evaluate compliance and approach speeds of passive level crossings.

Biofilms can cause severe problems to human health due to the high tolerance to antimicrobials; consequently, biofilm science and technology constitutes an important research field. Growing a relevant biofilm in the laboratory provides insights into the basic understanding of the biofilm life cycle including responses to antibiotic therapies. Therefore, the selection of an appropriate biofilm reactor is a critical decision, necessary to obtain reproducible and reliable in vitro results. A reactor should be chosen based upon the study goals and a balance between the pros and cons associated with its use and operational conditions that are as similar as possible to the clinical setting. However, standardization in biofilm studies is rare. This review will focus on the four reactors (Calgary biofilm device, Center for Disease Control biofilm reactor, drip flow biofilm reactor, and rotating disk reactor) approved by a standard setting organization (ASTM International) for biofilm experiments and how researchers have modified these standardized reactors and associated protocols to improve the study and understanding of medical biofilms.

Structural DNA nanotechnology utilizes synthetic or biologic DNA as designer molecules for the self-assembly of artificial nanostructures. The field is founded upon the specific interactions between DNA molecules, known as Watson-Crick base pairing. After decades of active pursuit, DNA has demonstrated unprecedented versatility in constructing artificial nanostructures with significant complexity and programmability. The nanostructures could be either static, with well-controlled physicochemical properties, or dynamic, with the ability to reconfigure upon external stimuli. Researchers have devoted considerable effort to exploring the usability of DNA nanostructures in biomedical research. We review the basic design methods for fabricating both static and dynamic DNA nanostructures, along with their biomedical applications in fields such as biosensing, bioimaging, and drug delivery.

Rationale and Objectives: The purpose of this study was to integrate web-based forms with a zero-footprint cloud-based Picture Archiving and Communication Systems (PACS) to create a tool of potential benefit to radiology research and education., Materials and Methods: Web-based forms were created with a front-end and back-end architecture utilizing common programming languages including Vue.js, Node.js and MongoDB, and integrated into an existing zero-footprint cloud-based PACS., Results: The web-based forms application can be accessed in any modern internet browser on desktop or mobile devices and allows the creation of customizable forms consisting of a variety of questions types. Each form can be linked to an individual DICOM examination or a collection of DICOM examinations., Conclusions: Several uses are demonstrated through a series of case studies, including implementation of a research platform for multi-reader multi-case (MRMC) studies and other imaging research, and creation of an online Objective Structure Clinical Examination (OSCE) and an educational case file., (Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The development of nanomachines able to operate at the nanoscale, performing complex tasks such as drug delivery, precision surgery, or cell detection, constitutes one of the most important challenges in nanotechnology. The principles that rule the nanoscale are completely different from the ones which govern the macroscopic world and, therefore, the collaboration of scientists with expertise in different fields is required for the effective fabrication of these tiny machines. In this review, the most recent advances carried out in the synthesis and application of nanomachines for diagnosis applications will be presented in order to provide a picture of their potential in the detection of important biomolecules or pathogens in a selective and controlled manner.

High contrast in X-ray medical imaging, while maintaining acceptable radiation dose levels to the patient, has long been a goal. One of the most promising methods is that of K-edge subtraction imaging. This technique, first advanced as long ago as 1953 by B. Jacobson, uses the large difference in the absorption coefficient of elements at energies above and below the K-edge. Two images, one taken above the edge and one below the edge, are subtracted leaving, ideally, only the image of the distribution of the target element. This paper reviews the development of the KES techniques and technology as applied to bio-medical imaging from the early low-power tube sources of X-rays to the latest high-power synchrotron sources. Applications to coronary angiography, functional lung imaging and bone growth are highlighted. A vision of possible imaging with new compact sources is presented., (Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Airborne allergic diseases (allergic asthma, rhinitis and conjunctivitis) have reached epidemic proportions and are a great burden for both society and individuals. Therefore we need to better understand the physiopathological mechanisms and to increase clinical research in these diseases. However, traditional outpatient studies are difficult and have number of limitations, in particular the variability of allergen exposure. Yet allergen provocation tests, especially bronchial challenges in asthma, are excellent tools to measure the efficiency of anti-allergic therapies. Environmental exposure chambers (EEC) allow the performance of controlled allergen provocation tests on a large scale with remarkable sensitivity, specificity and reproducibility. Moreover, they allow a precise collection of allergic symptoms, making them interesting tools for patho-physiological and clinical studies. During the last thirty years, they have assisted the study of anti-allergic therapies and provided data on their pharmacodynamic characteristics, particularly in allergic rhinitis. However, there are still no EEC tests centered on asthma. The EEC of Strasbourg (ALYATEC ® ) was developed to fulfill two objectives: to allow standardized allergenic and non-allergenic exposures with better control of the parameters than in other EEC and to offer a place to study asthma and anti-asthmatic therapies safely., (Copyright © 2018. Published by Elsevier Masson SAS.)

A happy coincidence brought Dr Markus Rimann from ZHAW Waedenswil together with Dr Andreas Meyer from the start-up FGen and PD Dr Emanuela Felley-Bosco, Molecular Oncologist at Zurich University Hospital, to develop a technology platform for the manufacture and high throughput analysis of single mesothelioma spheroids. Armin Picenoni, former student in Chemistry for the Life Sciences at ZHAW, confirmed everything in writing his Master Thesis on this Innosuisse project.

Competing Interests: Competing interests: None declared.

Intravital imaging has been increasingly employed in cell biology studies and it is becoming one of the most powerful tools for in vivo investigation. Although some protocols can be extremely complex, most intravital imaging procedures can be performed using basic surgery and animal maintenance techniques. More importantly, regular confocal microscopes - the same that are used for imaging immunofluorescence slides - can also acquire high quality intravital images and movies after minor adaptations. Here we propose minimal adaptations in stock microscopes that allow major improvements in different fields of scientific investigation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The diversity and huge omics data take biology and biomedicine research and application into a big data era, just like that popular in human society a decade ago. They are opening a new challenge from horizontal data ensemble (e.g., the similar types of data collected from different labs or companies) to vertical data ensemble (e.g., the different types of data collected for a group of person with match information), which requires the integrative analysis in biology and biomedicine and also asks for emergent development of data integration to address the great changes from previous population-guided to newly individual-guided investigations.Data integration is an effective concept to solve the complex problem or understand the complicate system. Several benchmark studies have revealed the heterogeneity and trade-off that existed in the analysis of omics data. Integrative analysis can combine and investigate many datasets in a cost-effective reproducible way. Current integration approaches on biological data have two modes: one is "bottom-up integration" mode with follow-up manual integration, and the other one is "top-down integration" mode with follow-up in silico integration.This paper will firstly summarize the combinatory analysis approaches to give candidate protocol on biological experiment design for effectively integrative study on genomics and then survey the data fusion approaches to give helpful instruction on computational model development for biological significance detection, which have also provided newly data resources and analysis tools to support the precision medicine dependent on the big biomedical data. Finally, the problems and future directions are highlighted for integrative analysis of omics big data.

The purpose of 3D bioprinting technology is to design and create functional 3D tissues or organs in situ for in vivo applications. 3D cell-printing, or additive biomanufacturing, allows the selection of biomaterials and cells (bioink), and the fabrication of cell-laden structures in high resolution. 3D cell-printed structures have also been used for applications such as research models, drug delivery and discovery, and toxicology. Recently, numerous attempts have been made to fabricate tissues and organs by using various 3D printing techniques. However, challenges such as vascularization are yet to be solved. This article reviews the most commonly used 3D cell-printing techniques with their advantages and drawbacks. Furthermore, up-to-date achievements of 3D bioprinting in in vivo applications are introduced, and prospects for the future of 3D cell-printing technology are discussed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 444-459, 2018., (© 2017 Wiley Periodicals, Inc.)

Generally, machine learning includes many in silico methods to transform the principles underlying natural phenomenon to human understanding information, which aim to save human labor, to assist human judge, and to create human knowledge. It should have wide application potential in biological and biomedical studies, especially in the era of big biological data. To look through the application of machine learning along with biological development, this review provides wide cases to introduce the selection of machine learning methods in different practice scenarios involved in the whole biological and biomedical study cycle and further discusses the machine learning strategies for analyzing omics data in some cutting-edge biological studies. Finally, the notes on new challenges for machine learning due to small-sample high-dimension are summarized from the key points of sample unbalance, white box, and causality.

Metabolomics aims to quantitatively measure small-molecule metabolites in biological samples, such as bodily fluids (e.g., urine, blood, and saliva), tissues, and breathe exhalation, which reflects metabolic responses of a living system to pathophysiological stimuli or genetic modification. In the past decade, metabolomics has made notable progresses in providing useful systematic insights into the underlying mechanisms and offering potential biomarkers of many diseases. Metabolomics is a complementary manner of genomics and transcriptomics, and bridges the gap between genotype and phenotype, which reflects the functional output of a biological system interplaying with environmental factors. Recently, the technology of metabolomics study has been developed quickly. This review will discuss the whole pipeline of metabolomics study, including experimental design, sample collection and preparation, sample detection and data analysis, as well as mechanism interpretation, which can help understand metabolic effects and metabolite function for living organism in system level.

After several decades of relatively modest use, in the last several years digital PCR (dPCR) has grown to become the new gold standard for nucleic acid quantification. This coincides with the commercial availability of scalable, affordable, and reproducible droplet-based dPCR platforms in the past five years and has led to its rapid dissemination into diverse research fields and testing applications. Among these, it has been adopted most vigorously into clinical oncology where it is beginning to be used for plasma genotyping in cancer patients undergoing treatment. Additionally, innovation across the scientific community has extended the benefits of reaction partitioning beyond DNA and RNA quantification alone, and demonstrated its usefulness in evaluating DNA size and integrity, the physical linkage of colocalized markers, levels of enzyme activity and specific cation concentrations in a sample, and more. As dPCR technology gains in popularity and breadth, its power and simplicity can often be taken for granted; thus, the reader is reminded that due diligence must be exercised in order to make claims not only of precision but also of accuracy in their measurements.

Traditionally, head fixation devices and recording cylinders have been implanted in nonhuman primates (NHP) using dental acrylic despite several shortcomings associated with acrylic. The use of more biocompatible materials such as titanium and PEEK is becoming more prevalent in NHP research. We describe a cost-effective set of procedures that maximizes the integration of headposts and recording cylinders with the animal's tissues while reducing surgery time. Nine rhesus monkeys were implanted with titanium headposts, and one of these was also implanted with a recording chamber. In each case, a three-dimensional printed replica of the skull was created based on computerized tomography scans. The titanium feet of the headposts were shaped, and the skull thickness was measured preoperatively, reducing surgery time by up to 70%. The recording cylinder was manufactured to conform tightly to the skull, which was fastened to the skull with four screws and remained watertight for 8.5 mo. We quantified the amount of regression of the skin edge at the headpost. We found a large degree of variability in the timing and extent of skin regression that could not be explained by any single recorded factor. However, there was not a single case of bone exposure; although skin retracted from the titanium, skin also remained adhered to the skull adjacent to those regions. The headposts remained fully functional and free of complications for the experimental life of each animal, several of which are still participating in experiments more than 4 yr after implant. NEW & NOTEWORTHY Cranial implants are often necessary for performing neurophysiology research with nonhuman primates. We present methods for using three-dimensional printed monkey skulls to form and fabricate acrylic-free implants preoperatively to decrease surgery times and the risk of complications and increase the functional life of the implant. We focused on reducing costs, creating a feasible timeline, and ensuring compatibility with existing laboratory systems. We discuss the importance of using more biocompatible materials and enhancing osseointegration., (Copyright © 2017 the American Physiological Society.)